Increasing the polyunsaturated fatty acid content of the diet leads to a long-term enhanced prostaglandin and thromboxane synthesis. We have shown a protective effect of high linoleic and high eicosapentaenoic acid diets in the partially nephrectomized rat, a model of progressive renal failure, and in an immunologic model of glomerulonephritis induced by apoferritin injection in the mouse. This and theoretical considerations on the potential effects of prostaglandins of the 1-series, of the 2-series, and of the 3-series lead us to propose a series of animal experiments with long-term objectives, the aims of which are: 1. To assess the role of dietary supplementation with three different polyunsaturated fatty acids in the prevention of diabetic nephropathy. The three fatty acids chosen are gammalinolenic acid (GLA) which is known to stimulate synthesis of PGs of the 1-series; linoleic acid (LA) which is known to stimulate synthesis of PGs of the 2-series; and eicosapentaenoic acid (EPA) which is known to stimulate synthesis of the PGs of the 3-series. 2. To assess the role of such dietary stimulation of prostaglandin synthesis in an experimental model of renal failure: the rat with streptozotocin-induced diabetes mellitus. 3. To determine whether beneficial effects of polyunsaturated fatty acid supplementation of the diet are mediated by prostaglandins and thromboxanes; also to assess the possible influences of the prostaglandins and thromboxanes on the adaptive mechanisms which lead to renal functional and morphologic changes in the diabetic environment. 4. To investigate the possible relationship between the PGs and TXs with other factors which are considered to be pathogenetically important in renal disease, such as the fibrinolytic system and plasma lipid composition.